Modification by levo-propranolol of tremors induced by harmine in mice

Summary It has been recently reported that the levo isomer of propranolol possesses anti-serotonin properties in animals. Since harmine-induced behavioural changes in mice are reported to be mediated through central serotonergic receptors, an attempt was made to test whether 1-propranolol would also modify harmine-induced responses by virtue of its antiserotonergic or anti-adrenergic property. The results indicated that 1- and dl-propranolol inhibited central serotonin receptor mediated responses to harmine in mice, a finding that is analogous to other recent observations.     

Modification by levo-propranolol of tremors induced by harmine in mice

It has been recently reported that the levo isomer of propranolol possesses anti-serotonin properties in animals. Since harmine-induced behavioural changes in mice are reported to be mediated through central serotonergic receptors, an attempt was made to test whether 1-propranolol would also modify harmine-induced responses by virtue of its anti-serotonergic or anti-adrenergic property. The results indicated that l- and dl-propranolol inhibited central serotonin receptor mediated responses to harmine in mice, a finding that is analogous to other recent observations.     

Inactivation of aldolase by X-rays

Riassunto È stata studiata in vitro l'inattivazione da raggi x dell'aldolasi dal muscolo di coniglio. Il rendimento di inattivazione corrisponde a 0,10 (molecule/100 ev) per concentrazioni comprese tra 10^–5 and 10^–6 M in tampone di fosfati 0,05M, pH 7. Il rendimento non subisce modificazioni di rilievo variando il pH da 6 a 8 o sostituendo al tampone l'acqua bidistillata. Il rendimento é ridotto da 4 a 6 volte in presenza di cisteamina, di cisteina o dei corrispondenti disolfuri in concentrazioni corrispondenti a 50 molecule per molecola di enzima. Coll'ioduro di sodio in concentrazione di 600:1 si ottiene una riduzione di 6 volte.     

Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters

Cancer cell resistance to chemotherapy is often mediated by overexpression of P-glycoprotein, a plasma membrane ABC (ATP-binding cassette) transporter which extrudes cytotoxic drugs at the expense of ATP hydrolysis. P-glycoprotein (ABCB1, according to the human gene nomenclature committee) consists of two homologous halves each containing a transmembrane domain (TMD) involved in drug binding and efflux, and a cytosolic nucleotide-binding domain (NBD) involved in ATP binding and hydrolysis, with an overall (TMD-NBD)2 domain topology. Homologous ABC multidrug transporters, from the same ABCB family, are found in many species such as Plasmodiumfalciparum and Leishmania spp. protozoa, where they induce resistance to antiparasitic drugs. In yeasts, some ABC transporters involved in resistance to fungicides, such as Saccharomyces cerevisiae Pdr5p and Snq2p, display a different (NBD-TMD)2 domain topology and are classified in another family, ABCG. Much effort has been spent to modulate multidrug resistance in the different species by using specific inhibitors, but generally with little success due to additional cellular targets and/or extrusion of the potential inhibitors. This review shows that due to similarities in function and maybe in three-dimensional organization of the different transporters, common potential modulators have been found. An in vitro 'rational screening' was performed among the large flavonoid family using a four-step procedure: (i) direct binding to purified recombinant cytosolic NBD and/or full-length transporter, (ii) inhibition of ATP hydrolysis and energy-dependent drug interaction with transporter-enriched membranes, (iii) inhibition of cell transporter activity monitored by flow cytometry and (iv) chemosensitization of cell growth. The results indicate that prenylated flavonoids bind with high affinity, and strongly inhibit drug interaction and nucleotide hydrolysis. As such, they constitute promising potential modulators of multidrug resistance.     

Modulation by polyamines of apoptotic pathways triggered by procyanidins in human metastatic SW620 cells

We showed previously that inhibition of polyamine catabolism with the polyamine oxidase inhibitor MDL 72527 (MDL) potentiates the apoptotic effects of apple procyanidins (Pcy) in SW620 cells. Here we report that Pcy caused an activation of the intrinsic apoptotic pathway through enhanced polyamine catabolism and mitochondrial membrane depolarization. MDL in the presence of Pcy caused a profound intracellular depletion of polyamines and exerted a protective effect on mitochondrial functions. MDL potentiation of Pcy-triggered apoptosis was reversed by addition of exogenous polyamines. In addition, MDL in combination with Pcy activated the extrinsic apoptotic pathway through enhanced TRAIL-death receptor (DR4/DR5) expression. Potentiation of Pcy-triggered apoptosis by MDL was inhibited when cells were exposed to specific inhibitors of DR4/DR5. These data indicate that the depletion of intracellular polyamines by MDL in the presence of Pcy caused a switch from intrinsic to extrinsic apoptotic pathways in human colon cancer-derived metastatic cells. Received 15 January 2008; received after revision 19 February 2008; accepted 7 March 2008     

Nuclear degeneration induced by chlortetracycline

Summary After application of chlortetracycline to plants, a degeneration of nuclei, manifested by dilatation and vacuolation of the nuclear membrane, occurs in the mesophyll cells of the sunflower plant.     

Enhancement by caffeine of sister-chromatid exchange frequency induced by antineoplastic agents in human lymphocytes

Summary The SCE frequency induced by Thiotepa and the effect of this antineoplastic drug in combination with caffeine have been studied in cultures of human peripheral blood. Caffeine was found to enhance SCE and breakage frequencies induced by Thiotepa in human lymphocytes.Acknowledgment. I am deeply grateful to Dr M.J.W. Faed, for stimulating discussions, guidance and constructive criticism. This paper is a part of my Ph.D. thesis submitted to Dundee University.     

Signal regulation by family conspiracy

The signal regulating proteins (SIRPs) are a family of ubiquitously expressed transmembrane glycoproteins composed of two subgroups: SIRPα and SIRPβ, containing more than ten members. SIRPα has been shown to inhibit signalling through a variety of receptors including receptor tyrosine kinases and cytokine receptors. This function involves protein tyrosine kinases and is dependent on immunoreceptor tyrosine-based inhibition motifs which recruit key protein tyrosine phosphatases to the membrane. Negative regulation by SIRPα may also involve its ligand, CD47, in a bi-directional signalling mechanism. The SIRPβ subtype has no cytoplasmic domain but instead associates with at least one other transmembrane protein (DAP-12, or KARAP). DAP-12 possesses immunoreceptor tyrosine-based activation motifs within its cytoplasmic domain that are thought to link SIRPβ to activating machinery. SIRPα and SIRPβ thus have complementary roles in signal regulation and may conspire to tune the response to a stimulus. Received 6 July 2000; revised 2 August 2000; accepted 5 August 2000     

Activation of complement by trypanosomes

Summary Factors exhibiting anti-complementary activity released from trypanosomes after incubation at 20°C were described. The active material was shown to consume the first component of bovine complement. While the anticomplementary factor(s) from T. lewisi could activate bovine, human and guinea pig complement, the factor(s) from T. congolense was observed to activate bovine complement, but not guinea pig and only slightly human complement. The roles of complement activating factor(s) of trypanosomes in the pathology of the disease are discussed.This project is supported by National Research Council of Canada grant A 0068 and a grant from the International Development Research Centre.     

Robust seasonal adjustment by Bayesian modelling

Akaike's BAYSEA approach to seasonal decomposition is designed to capture the respective merits of several pre-existing adjustment techniques. BAYSEA is computationally efficient, requires only weak assumptions about the data-generating process, and is based on solid inferential (namely, Bayesian) foundations. We present a model similar to that used in BAYSEA, but based on a double exponential rather than a Gaussian error model. The resulting procedure has the advantages of Akaike's method, but in addition is resistant to outliers. The optimal decomposition is obtained rapidly using a sparse linear programming code. Confidence bands and predictive intervals can be obtained using Gibbs sampling.     

Inhibition of liver fructose 1,6-bisphosphatase activity by Zn2+: Reversal by imidazole pyruvate

Summary Imidazole pyruvate was found to be a very potent natural chelating agent in reversing the inhibition of liver fructose 1,6-bisphosphatase activity by Zn²⁺. This metabolite may play a physiological role in gluconeogenesis.This work was supported by grant RR-8006 from the General Research Branch, Division of Research Resources, NIH, USA.     

Hypoaldosteronism in piglets induced by carbadox

An exploratory study was made of the mechanisms underlying the toxic action of carbadox in young pigs: dehydration, loss of appetite and at autopsy seemingly specific and selective structural alterations of the glomerular zone of the adrenal cortex. Administration of carbadox in the feed, in dosages of 150 ppm (approximately 6 mg X kg-1 b. wt X day-1) caused a rapid decline in the plasma aldosterone levels (to 10% of control) followed by significant changes in the sodium and potassium levels in blood. Characteristic for the toxic action of carbadox are the rapid and seemingly selective and specific alterations in the aldosterone-releasing zona glomerulosa of the adrenals. Our results indicate that with carbadox a functional and possibly reversible extirpation of the adrenal zona glomerulosa can be achieved in pigs.     

Light-driven DNA repair by photolyases

DNA photolyases are highly efficient light-driven DNA repair enzymes which revert the genomedamaging effects caused by ultraviolet (UV) radiation. These enzymes occur in almost all living organisms exposed to sunlight, the only exception being placental mammals like humans and mice. Their catalytic mechanism employs the light-driven injection of an electron onto the DNA lesion to trigger the cleavage of cyclobutane- pyrimidine dimers or 6-4 photoproducts inside duplex DNA. Spectroscopic and structural analysis has recently yielded a concise view of how photolyases recognize these DNA lesions involving two neighboring bases, catalyze the repair reaction within a nanosecond and still achieve quantum efficiencies of close to one. Apart from these mechanistic aspects, the potential of DNA photolyases for the generation of highly UV-resistant organisms, or for skin cancer prevention by ectopical application is increasingly recognized. Received 29 September 2005; received after revision 30 November 2005; accepted 15 February 2006     

Time-series analysis supported by power transformations

This paper presents some procedures aimed at helping an applied time-series analyst in the use of power transformations. Two methods are proposed for selecting a variance-stabilizing transformation and another for bias-reduction of the forecast in the original scale. Since these methods are essentially model-independent, they can be employed with practically any type of time-series model. Some comparisons are made with other methods currently available and it is shown that those proposed here are either easier to apply or are more general, with a performance similar to or better than other competing procedures.     

膜分离处理印染废水研究进展

印染废水具有水量大、色度高、成分复杂、环境污染严重等特点。膜分离技术处理印染废水具有选择性好、生产效率高和处理成本低等特点。基于对近年来的文献调研,综述了膜分离技术在印染废水处理中的研究进展情况,指出了膜分离法处理印染废水还存在的主要问题和未来发展方向,并对膜分离技术处理印染废水应用前景作了展望。     

Fibrillation of tropoelastin induced by proteoglycan

Summary Electrostatic interaction between tropoelastin, the native precursor of elastin, and proteoglycan results in tropoelastin fibrillation. The finding suggests a possible involvement of proteoglycans in elastogenesis.     

Inhibition of ovulation in rats by antagonists to serotonin and by a new tricyclic compound

Summary The ovulation inhibiting activity in adult rats of the 5HT-antagonists cyproheptadine, mianserin and methysergide is shown. Furthermore the activity of a newly synthetized Cycloheptathiophenederivative, compound 26–921, which inhibits LH-secretion and consequently ovulation, is described.     

Host recognition by toxigenic plant pathogens

Certain fungal pathogens release host-selective (or host-specific) toxins (HST) as a host recognition factor during spore germination at the infection site on plants. Prior to penetration of the pathogen into its host, the released toxin specifically binds to a putative receptor on the host cells and initiates signaling mechanisms leading to pleiotropic effects on cells. Of these, the crucial one negates the general and inducible defense reactions of the cells. This is accomplished by a signal from the HST, which is transduced through a path way at or near the step of plasma membrane modulation, which is directly or indirectly triggered by the HST. This mechanism operates even though the toxin may affect mitochondria or chloroplasts as the primary target organelle. The fungal spore is able to penetrate the so-called 'narcotized cell' and completes the initial colonization of the host. The host recognition process may take place without necessitating host cell death, even in the case of perthophytic parasites. At the molecular level, HST-mediated recognition of the host by a pathogen requires strict stereochemical precision like a lock and key.     

Endogenous pyrogen formation by human blood monocytes stimulated by polyriboinosinic acid:Polyribocytidylic acid

The pyrogenic response to supernatants from human blood monocytes stimulated with polyriboinosinic acid:polyribocytidylic acid (poly I:C) was characteristic of a response to endogenous pyrogen in that it was brief and monophasic, and was destroyed by heating the supernatants at 70°C for 30 min. Pyrogen production was unimpaired when the incubations were carried out in the presence of cycloheximide (50 g/ml; an inhibitor of protein synthesis) or indomethacin (50 g/ml; an inhibitor of prostaglandin synthesis). Also, neither interferon, interleukins, tumor necrosis factor nor prostaglandin E₂ were detectable in the supernatants from the poly I:C-stimulated human monocytes.